This proposal will continue ongoing research into the function of the autonomic nervous system during anesthetic administration by examining the influence of an intravenous anesthetic adjuvant (midazolam) on sympathetic function in humans. These studies will also assess the effects of two volatile anesthetics (isoflurane and desflurane), as well as midazolam on vascular smooth muscle by employing the isolated human forearm model. In the proposed research, the endothelium in the forearm arterial vessels will be manipulated through brachial artery infusions of acetylcholine (to stimulate the EDRF/NO system) and NG-monomethyl L-arginine (L-NMMA) to block the synthesis of EDRF/NO before and during administration of either volatile or intravenous anesthetics. Additional studies will be carried out to determine if volatile anesthetics alter either arterial or venous vascular responsiveness to the a-1 agonist, phenylephrine. The effects of isoflurane and desflurane on two human models where endothelial function is enhanced (due to high estrogen levels) or impaired (due to aging) will also be examined.